Curcumin Yakagadzirwa J-147 Bata AD, Anti-kukwegura, Kushungurudzika Dambudziko (MDD)

J-147 Ongororo

Curcumin ipolyphenol uye chinhu chinoshanda cheTurmeric neGinger.Curcumin ine zvakawanda zvakabvumidzwa mabhenefiti ekurapa zvirwere zvakawanda, asi nekuda kwekusakwanisa kwayo kuyambuka Ropa-Brain Chipingamupinyi (BB), pane zviripo zvakajeka.

Chaizvoizvo, J147 (CAS:1146963-51-0) inotorwa neCurcumin uye Cyclohexyl-Bisphenol A (CBA) icho chine simba neurogenic uye neuroprotective mushonga. Yakagadzirirwa kushandiswa kwekurapa mamiriro eurodegenerative mamiriro ane chekuita nekukwegura. J147 inogona kuyambuka iyo BBB ichipinda muuropi (yakasimba) uye inokonzeresa neuronal stem masero ekugadzira.

Kusiyana nemishonga yazvino inogamuchirwa yeAlzheimer's Disease, J147 haisi acetylcholinesterase inhibitor kana phosphodiesterase inhibitor, asi inowedzera kugona nekurapwa kwenguva pfupi.

Mune ino posvo, isu tichakurukura kuti iyo curcumin inogadzirwa J147 inobata sei Alzheimer's Disease (AD), hombe kushungurudzika kusagadzikana (MDD) uye Anti-kukwegura.

Hezvino zvirimo:

1. Dzidza zvakawanda nezve J-147 Basa (Mechanism)
2. Kurumidza Kuona Kubatsirwa kweJ-147
3. J-147 Bata Chirwere cheAlzheimer (AD)
4. J-147 Bata Dambudziko Rekukwegura
5. J-147 Bata Major kushungurudzika kusagadzikana (MDD)
6. Zvimwe Ongororo Nezve J-147
7. Kwokutenga J-147 Powder

Dzidza zvakawanda nezve J-147 Basa (Mechanism)

Kusvikira 2018, iyo J-147 mhedzisiro pane iyo sero yakaramba isinganzwisisike kusvikira iyo Salk Institute Neurobiologists yakanzwisisa dambanemazwi. Mushonga unoshanda nekusunga kuATP synthase. Iyi mitochondrial protein inogadzirisa kugadzirwa kwemagetsi esimba, nekudaro kudzora kukwegura Kuvapo kweJ-147 kuwedzera muhurongwa hwevanhu kunodzivirira huturu hunosanganidzana nezera hunokonzerwa nekusagadzikana kwemitochondria uye kuwanda kweATP.

J-147 mashandiro ekuita achawedzerawo iwo mazinga eanosiyana-siyana maurotransmitter anosanganisira NGF neBDNF. Kunze kwezvo, inoshanda pamatanho e beta-amyloid, ayo anogara akakwirira pakati pevarwere vane Alzheimer's uye dementia. J-147 mhedzisiro inosanganisira kudzora kufambira mberi kweAlzheimer's, kudzivirira kushomeka kwendangariro, uye kuwedzera kugadzirwa kwemasero emitsipa.

Kurumidza Kuona Kubatsirwa kweJ-147

❶ Inovandudza Mitochondrial Basa Uye Hurefu

❷ Inodzivirira chirwere cheAlzheimer

❸ Inovandudza Ndangariro

❹ Inokura Iyo Brain

❺ Inodzivirira maNeuron

❻ Inogona Kuvandudza Chirwere cheshuga

Ights Kurwisa Kurwadziwa Uye Neuropathy

❽ May Kuvandudza Kunetseka

J-147 Bata Chirwere cheAlzheimer (AD)

J-147 uye AD: kumashure 

Parizvino, iyo huru yekuwana zvinodhaka paradigm yezvirwere zveeurodegenerative yakavakirwa pamusoro pehukama hwehukama hwega hwechirwere chakanangana nechinangwa. Yechirwere cheAlzheimer (AD), chinotariswa iamyloid beta peptide (Ass) iyo inopindirana neyemhuri yeAlzheimer's chirwere chirwere. Nekudaro, tichipiwa zera iri ndiyo njodzi huru yeAD, takaongorora imwe nzira yekutsvaga zvinodhaka iyo yakavakirwa pakubudirira mune akawanda maseru mutsika mamodheru ezvezera-zvine chekuita nezvirwere kwete kungoita amyloid metabolism. Tichishandisa nzira iyi, isu takaona yakasarudzika ine simba, nemuromo inoshanda, neurotrophic molecule iyo inofungisa ndangariro mune zvakajairwa makonzo, uye inodzivirira kurasikirwa kwemapuroteni e synaptic uye kudonha kwekuziva mune yemagetsi AD mbeva modhi.

J 147 uye AD: Ongororo yekutora kubva paMakonzo

NHEURI: Kunyangwe makore ekutsvaga, hapana chirwere-chinoshandura mishonga yeAlzheimer's chirwere (AD), inouraya, yezera-inoenderana nezera neurodegenerative kusagadzikana. Kuongororwa kweanogona kurapwa ekurapa mumakonzo emhando dzeAD kazhinji aivimba nekuyedza makomputa chirwere chisati chavepo, nekudaro modelling yekudzivirira chirwere kwete kuchinjisa chirwere. Uyezve, iyi nzira yekuongorora haina kuratidzira kiriniki yevarwere veAD iyo inogona kutsanangura kutadza kududzira macompound anoonekwa seanobatsira mumhando dzemhuka kune chirwere chinoshandura makomponi mumakiriniki ekuedzwa. Zviripachena nzira iri nani yeku pre-kiriniki yekuongorora zvinodhaka zveAD inodiwa

METHODZO: Kuti tinyatso kuratidza mamiriro emakiriniki, isu takashandisa imwe nzira yekutarisa inosanganisira kurapwa kweAD mbeva padanho rechirwere apo hutachiona hwakatofambira mberi. Vakwegura (makumi maviri-mwedzi wemwedzi) transgenic AD mbeva (APP / swePS20DeltaE1) vakapihwa yakasarudzika ine simba, yemuromo inoshanda, yekumusoro yekurangarira uye neurotrophic molecule inonzi J9. Kufungisisa maitiro ekuedza, histology, ELISA uye Western blotting zvakashandiswa kuyedza mhedzisiro yeJ147 mundangariro, amyloid metabolism uye neuroprotective nzira. J147 yakaferefetwawo mune imwe scopolamine-inosimudzira modhi yekukanganisa ndangariro muC147Bl / 57J mbeva uye ichienzaniswa neepostezez. Tsanangudzo pane pharmacology uye chengetedzo yeJ6 inosanganisirwa.

RESULTS: Dhata yakapihwa pano inoratidza kuti J147 ine kugona kununura kushomeka kwekuziva kana ichigadziriswa panguva yekupedzisira muchirwere. Iko kugona kweJ147 kunatsiridza ndangariro mune akura AD mbeva kunoenderana nekuiswa kwayo kweiyo neurotrophic zvinhu NGF (nerve kukura chinhu) uye BDNF (huropi hwakatora neurotrophic factor) pamwe neakawanda BDNF-anoteerera mapuroteni ayo akakosha pakudzidza nekurangarira. Kufananidza pakati peJ147 uye donepezil muiyo scopolamine modhi kwakaratidza kuti nepo ese maviri macompound angafananidzwa pakununura pfupi pfupi ndangariro, J147 yaive yepamusoro pakununura nzvimbo yekurangarira uye musanganiswa wevaviri wakashanda zvakanyanya kune mamiriro uye cued ndangariro.

Mhedziso paJ-147 yeAD

J147 chinhu chinonakidza chitsva chine simba kwazvo, chakachengeteka muzvidzidzo zvemhuka uye nemuromo unoshanda. J147 ingangoita AD yekurapa nekuda kwekugona kwayo kupa nekukurumidza kuziva kubatsirwa, uye zvakare ine mukana wekumira uye pamwe ungadzorere kuwedzera kukura kwezvirwere mumhuka dzinoratidzira sezvakaratidzwa mune izvi zvidzidzo.

J-147 Bata Dambudziko Rekukwegura

J-147 uye Anti-kukwegura: Mamiriro ezvinhu 

Mbeva dzakarapwa neJ147 dzaive nendangariro zvirinani uye kugona, mishonga yeropa ine hutano muuropi uye nezvimwe zvinoitwa zvemuviri…

"Pakutanga, kurudziro yaive yekuyedza mushonga uyu mune yemhando yemhuka yaive yakafanana ne99% yezvirwere zveAlzheimer," anodaro Antonio Currais, nhengo yePurofesa David Schubert's Cellular Neurobiology Laboratory kuSalk. "Hatina kufanotaura kuti tichaona rudzi urwu Anti-aging asi J147 yakaita kuti mbeva dzekare dziratidzike sedziri diki, zvichibva pamitezo yakati wandei yemuviri. ” "Kunyange mishonga yakawanda yakagadzirwa mukati memakore makumi maviri apfuura yakanangana nechidimbu cheamyloid muuropi (chinova chiratidzo chechirwere), hapana chakaratidza kuti chinoshanda mukiriniki," anodaro Schubert.

Makore akati wandei apfuura, Schubert nevamwe vake vakatanga kusvika pakurapwa kwechirwere ichi kubva nekona nyowani. Panzvimbo pekutarisa amyloid, iyo lab yakasarudza zero mukati meiyo huru njodzi yekukonzeresa kwechirwere - kuchembera. Vachishandisa maseru-akavakirwa masikirini kurwisa huchembera-hwakabatana huro huturu, vakagadzira J147

Pakutanga, timu yacho yakaona kuti J147 yaigona kudzivirira uye kutodzosera kurasikirwa ndangariro uye chirwere cheAlzheimer mumakonzo ane vhezheni yefomu yakagara nhaka yeAlzheimer's, inonyanya kushandiswa mbeva modhi. Nekudaro, iri fomu rechirwere rinongova neinenge 1% yezviitiko zveAlzheimer's. Kune vamwe vese, kuchembera ndiyo inonyanya kukonzera njodzi, anodaro Schubert. Chikwata ichi chaida kuongorora zvinokonzereswa nemumiriri wemishonga parudzi rwe mbeva dzinokura nekukasira uye nekuona vhezheni yedhementia iyo yakafanana zvakanyanya nedambudziko revanhu rine chekuita nezera.

J-147 uye Anti-kukwegura: Ongororo yekutsvaga kuongororwa paMakonzo

Mune rino basa razvino, vaongorori vakashandisa seti yakazara yemayedzo kuyera kutaura kwemajini ese muuropi, pamwe neanopfuura mazana mashanu mamorekuru akabatanidzwa nemetabolism muuropi neropa remapoka matatu emakonzo anokurumidza kuchembera. Iwo matatu mapoka emakonzo anokurumidza kuchembera aisanganisira imwe seti yaive diki, imwe seti yaive yekare uye imwe seti yaive yekare asi yakapihwa J500 sezvavanokwegura.

Iyo mbeva dzekare dzakatambira J147 dzakaita zvirinani pane ndangariro uye kumwe kuyedzwa kwekucherechedzwa uye zvakare yakaratidza mafambiro akasimba emota. Iyo mbeva dzakarapwa neJ147 dzaivewo nemasaini mashoma ezviratidzo zveAlzheimer's muhuropi hwavo. Zvakakosha, nekuda kweiyo yakawanda dhata yakaunganidzwa pamapoka matatu emakonzo, zvaive zvichikwanisa kuratidza kuti akawanda maficha egeneti kutaura uye metabolism mumakonzo ekare akadyiswa J147 aive akafanana chaizvo neaya emhuka diki. Izvi zvaisanganisira mamaki ekuwedzera simba metabolism, kuderedzwa kwehuropi kuzvimba uye kuderedzwa kwehuwandu hweakisi yakasanganiswa yemafuta acids muuropi.

Chimwe chiitiko chakakosha ndechekuti J147 yakadzivirira kubuda kweropa kubva kuma microvessels muhuropi hwemakonzo ekare. "Mitsipa yeropa yakakuvara chinhu chinozivikanwa nekukwegura, uye muAlzheimer's, inowanzoitika zvakanyanya," anodaro Currais.

Mhedziso paJ-147 yedambudziko rekukwegura

Mice dzakadyiswa J147 dzaive dzawedzera simba metabolism uye dzakadzora hutachiona kuzvimba.Vatsvaguriri vakawana kuti muyedzo wekuedza mushonga anonangana nekurwisa chirwere cheAlzheimer, chinonzi J147, ane hondo isingatarisirwi. anti-kukwegura mhedzisiro mumhuka.

Chikwata kubva kuSalk Institute chakaratidza kuti mukwikwidzi wemushonga akashanda nemhando yegonzo yekukwegura isingawanzoshandiswa mukutsvaga kweAlzheimer. Kana idzi mbeva dzakarapwa neJ147, vaive nekurangarira kuri nani uye kugona, mitsipa yeropa ine hutano muhuropi uye nezvimwe zvakagadziriswa zvemuviri.

J-147 Bata Major kushungurudzika kusagadzikana (MDD)

J-147 uye MDD: kumashure

Major depression disorder (MDD) chirwere chakakomba chepfungwa chakanangana nekushomeka kwemonoamine neurotransmitters, kunyanya kune zvakasarudzika zve5-HT (5-hydroxytryptamine, serotonin) uye ayo anogamuchira. Chidzidzo chedu chekare chakaratidza kuti kurapwa kwakanyanya neruzivo curcumin yakabva J147 yakaratidza antidepressant-senge mhedzisiro nekuwedzera huropi hwakatorwa neurotrophic factor (BDNF) mwero mune hippocampus yemakonzo. Chidzidzo chazvino chakawedzera pane zvatakambowana uye tikatsvaga antidepressant-senge mhedzisiro yekurapa kwakanyanya kweJ147 kwemazuva matatu muhurume ICR mbeva uye zvingaite zvinoenderana ne3-HT5A uye 1-HT5B receptors uye yakadzika cAMP-BDNF kuisa chiratidzo.

J-147 uye MDD: Ongororo yekutora kuongororwa paMakonzo

Nzira: J147 pamiyero ye1, 3, uye 9 mg / kg (kuburikidza gavage) yakapihwa kwemazuva matatu, uye nguva yekurwisa-kusagadzikana mukumanikidza kushambira uye kumiswa kwekuyedzwa kwemuswe (FST neTST) yakanyorwa. Iyo radioligand inosunga assay yakashandiswa kuona hukama hweJ3 kusvika 147-HT5A uye 1-HT5B receptor. Uyezve, 1-HT5A kana 1-HT5B agonist kana anopikisa akashandiswa kuona kuti ndeipi 1-HT receptor subtype inobatanidzwa mune antidepressant-senge mhedzisiro yeJ5. Iwo ekudzika ezasi ekuratidzira mamorekuru akadai seCAMP, PKA, pCREB, uye BDNF zvakaverengerwawo kuona mashandiro ekuita.

Results: Mhedzisiro yacho yakaratidza kuti kurapa kwakanyanya kweJ147 kwakadzora zvinoshamisa nguva yekusafamba mune zvese FST uye TST nenzira inoenderana nedosi. J147 yakaratidza kubatana kwakanyanya mu vitro kune 5-HT1A receptor yakagadzirirwa kubva kumakonzo cortical tishu uye yaive shoma kune 5-HT1B receptor. Iyi mhedzisiro yeJ147 yakavharirwa nekufanobata pamwe neiyo 5-HT1A anopikisa NAD-299 uye yakawedzeredzwa ne5-HT1A agonist 8-OH-DPAT. Zvisinei, 5-HT1B mutevedzeri wemupikisi NAS-181 haana kuchinja nekuonga migumisiro yeJ147 pane kuora mwoyo-kufanana nemafambiro. Uyezve, kufungidzira kweNAD-299 kwakavhara J147-kwakakonzera kuwedzera mumisasa, PKA, pCREB, uye kutaura kweBDNF muhippocampus, nepo 8-OH-DPAT yakawedzera mhedzisiro yeJ147 pane aya mapuroteni.

Mhedziso paJ-147 yeMajuru kushushikana kwepfungwa (MDD)

Mhedzisiro yacho inoratidza kuti J147 inokonzeresa inokurumidza antidepressant-senge mhedzisiro panguva yemazuva matatu ekurapwa nguva pasina kukonzera kushivirira kwemishonga. Iyi mhedzisiro inogona kupindirana ne3-HT5A-inoenderana nekambi / PKA / pCREB / BDNF kusaina.

Zvimwe Ongororo Nezve J-147

-T-006: Maitiro Ekuita Iyi Yakagadziridzwa Imwe nzira kuna J-147

147 JXNUMX phenyl hydrazide inotorwa kubva kune yakasikwa komputa curcumin.

147 J2.5 ine hafu yeupenyu ye1.5 hrs muuropi, 4.5 hrs muplasma, 4min mune microsomes yevanhu, uye <XNUMXmin mune mbeva microsomes.

※ Chisingaperi kurapwa nemuromo neJ147 kwakadzivirira iyo sciatic nerve kubva mukufambira mberi kwechirwere cheshuga-inokonzeresa kudzora kweiyo yakakura myelinated fiber conduction velocity nepo imwe doses yeJ147 nekukurumidza uye nekukurumidza kuchinjika yakagadziriswa-yekubata allodynia.

147 JXNUMX kurapwa pasi-inodzorwa BACE, nokudaro ichiwedzera APP (isina kunaka APP cleavage pakupedzisira inopa kukwira kune Aβ).

Mit Iyo mitochondrial α-F1 subunit yeATP synthase (ATP5A) sehukama hwehukama hweJ147, puroteni yakambodzidzwa mumamiriro ekukwegura… ine dosi inoenderana nekudzivirirwa paATP5a.

147 JXNUMX yakadzorera iwo mazinga eacylcarnitines anoratidza maitiro akanaka pane mitochondrial dynamics.

MuNMDA receptors, T-006 inhibits yakawandisa Ca2 + kubuda.

※ T-006 ine basa rekudzivirira mune ino sisitimu kuburikidza neyese inodzivirira MAPK / ERK nzira uye kudzoreredza PI3-K / Akt nzira.

※ Zvimwe zvigadzirwa zvakaita se3j (dicyanovinyl-yakatsiviwa J147 analogue) inogona kudzvinyirira oligomerization uye fibrillation ye β-amyloid peptides uye inodzivirira maseru e-neuronal kubva ku-y-amyloid-inosimudzira cytotoxicity.

Kupi Kwokutenga J-147 Powder?

Hunhu hweiyi nootropic ichiri pfupa rekukakavara asi hazvizokutadzise kuwana zvigadzirwa zviri pamutemo. Mushure mezvose, J-147 Alzheimer's kliniki miedzo iri kuenderera. Unogona kutenga hupfu muzvitoro zvepamhepo sezvo iwe uchiwana mukana wekuenzanisa mitengo yeJ-147 kune vatengesi vakasiyana. Nekudaro, iwe unofanirwa kuve nechokwadi chekutenga-tenderera kubva kune vanoshanda vatengesi vane yakazvimirira marabhoritari kuyedzwa.

Kana iwe uchida zvimwe J-147 inotengeswa, tarisa nechitoro chedu. Isu tinopa akawanda nootropics pasi pehunhu kudzora. Unogona kutenga muhuwandu kana kutenga kamwechete zvichienderana nechinangwa chako chepfungwa. Ziva kuti, J-147 mutengo unoshamwaridzika chete kana iwe ukatenga muhuwandu hwakawanda.

Reference

[1] Asati a M, et al. Iyo neurotrophic komputa J147 inodzosera kukanganisika kwekukanganisa mune vakwegura chirwere cheAlzheimer mbeva. Alzheimers Res Ther. 2013 Chivabvu 14; 5 (3): 25.

[2] Chen Q, et al. Iyo inoverengeka neurotrophic mushonga wekuziva kugadzirisa uye chirwere cheAlzheimer. PLoS Imwe. 2011; 6 (12): e27865.

[3] Currais A, Goldberg J, Farrokhi C, Chang M, Pamberi M, Dargusch R, Daugherty D, Armando A, Quehenberger O, Maher P, Schubert D: Iyo yakazara multomics nzira yekunzwisisa hukama pakati pekukwegura uye kuora mwoyo. Kukwegura (Albany NY). 2015 Mbudzi; 7 (11): 937-55. doi: 10.18632 / kuchembera.100838. [PubMed: 26564964]

[4] Daugherty DJ, Marquez A, Calcutt NA, Schubert D: Inoverengeka curcumin inogadzirwa yekurapa chirwere cheshuga neuropathy. Neuropharmacology. 2018 Kukadzi; 129: 26-35. doi: 10.1016 / j.neuropharm.2017.11.007. Epub 2017 Mbudzi 6. [PubMed: 29122628]

[5] J. Goldberg, A. Currais, M. Asati, W. Fischer, C. Chiruta, E. Ratliff, D. Daugherty, R. Dargusch, K. Finley, PB Esparza-Molto, JM Cuezva, P. Maher, M. Petrascheck, D. Schubert

[6] Solomon B (Gumiguru 2008). "Filamentous bacteriophage seinovhura yekurapa chishandiso cheAlzheimer's chirwere kurapwa". Zvinyorwa zveAlzheimer's Disease. 15 (2): 193–8. PMID 18953108.

[7] Wang M, et al. Iyo yekutanga synthesis ye [11C] J147, nyowani inogona kuita PET mumiriri wekufungidzira kwechirwere cheAlzheimer. Bioorg Med Chem Lett. 2013 Ndira 15; 23 (2): 524-7.

[8] Asati a M, et al. Kusarudza kugona neurogenic senge imwe nzira yeAlzheimer's chirwere chinowanikwa. Alzheimers Dement. 2016 Jun; 12 (6): 678-86.